17-12901233-A-G

Position:

• chr17-12901233-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014859.6(ARHGAP44):​c.198+4722A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 151,994 control chromosomes in the GnomAD database, including 1,989 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1989 hom., cov: 31)
• Consequence: ARHGAP44 NM_014859.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59

Genes affected

ARHGAP44 (HGNC:29096): (Rho GTPase activating protein 44) Enables phospholipid binding activity. Predicted to be involved in several processes, including modification of dendritic spine; negative regulation of Rac protein signal transduction; and regulation of plasma membrane bounded cell projection organization. Located in leading edge membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARHGAP44 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP44	NM_014859.6	c.198+4722A>G		intron_variant		ENST00000379672.10	NP_055674.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP44	ENST00000379672.10	c.198+4722A>G		intron_variant		1	NM_014859.6	ENSP00000368994.5

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19331 AN: 151876 Hom.: 1986 Cov.: 31

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.0491

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0473

Gnomad OTH AF: 0.117

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19352 AN: 151994 Hom.: 1989 Cov.: 31 AF XY: 0.130 AC XY: 9645 AN XY: 74294

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.0890

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.0491

Gnomad4 NFE AF: 0.0472

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0651 Hom.: 899

Bravo AF: 0.134

Asia WGS AF: 0.266 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7209847; hg19: chr17-12804550;